Compositions for coronavirus infection treatment and/or prevention

Abstract

A composition includes a compound for treating and/or preventing a coronavirus infection in a subject. The coronavirus is severe acute respiratory syndrome coronavirus (SARS-CoV)-2, SARS-CoV-1, or Middle East respiratory syndrome coronavirus (MERS-CoV). Methods include treating and/or preventing a coronavirus infection in a subject by administering the composition to the subject.

1 . A method for treating a coronavirus infection in a subject in need thereof or avoiding onset of a coronavirus infection in a statistically significant portion of subjects in need thereof, comprising administering to the subject or subjects a composition comprising a compound selected from the group consisting of compounds indicated in Table 2 and Table 1. 
     
     
         2 . The method of  claim 1 , wherein said compound is a compound selected from the group consisting of LY2228820, NSC319726, polidocanol, Amuvatinib (MP-470), Tyrphostin AG 879 (AG 879), GSK2606414, AI-10-49, VLX600, Ethaverine, alvocidib, Cycloheximide, Cetylpyridinium, thioguanosine, Dapivirine (TMC120), Papaverine, Tanaproget, Octenidine, Almitrine, Sorafenib, ZK-93423, Thimerosal, Regorafenib (BAY 73-4506), Chlormidazole, ravuconazole, Methylene Blue, Mibampator, homoharringtonine, hematoporphyrin, LGK-974, Posaconazole, Ketoconazole, Nelfinavir, JTE-013, Bentamapimod, R05126766 (CH5126766), Lonafarnib (SCH66336), Apixaban, Pexidartinib, drotaverine, LDE225 (NVP-LDE225, Erismodegib, PFK-015, Avatrombopag, 3′-fluorobenzylspiperone, Etifoxine, Avasimibe (CI-1011), Lopinavir (ABT-378), DCPIB, PH-797804, flunarizine, Loteprednol etabonate, lidoflazine, BP-897, Cloconazole, PF-670462, Oxiconazole, AMG-9810, Brexpiprazole, talmapimod, Adoprazine, CC-223, Harringtonine, Barnidipine HCl, vatalanib, OSI-906 (Linsitinib), Idarubicin, Acrylflavine, Basimglurant, NNC-05-2090, Proflavine, Evacetrapib (LY2484595), LY335979 (Zosuquidar trihydrochloride), prenylamine, Fosaprepitant, Mefloquine, SB-657510, P276-00, PD-102807, dexniguldipine, ABC294640, Cyclosporine, and CGP-71683. 
     
     
         3 . The method of  claim 1 , wherein said coronavirus is a beta-coronavirus. 
     
     
         4 . The method of  claim 1 , wherein said coronavirus is severe acute respiratory syndrome coronavirus (SARS-CoV)-2, SARS-CoV-1, or Middle East respiratory syndrome coronavirus (MERS-CoV). 
     
     
         5 . The method of  claim 1 , wherein said coronavirus is SARS-CoV-2. 
     
     
         6 . The composition of  claim 1 , wherein said subject is a human. 
     
     
         7 . The method of  claim 1 , wherein said treating and/or preventing comprises inhibition of coronavirus replication. 
     
     
         8 . The method of  claim 1 , wherein said treating and/or preventing comprises inhibition of cell lysis by said coronavirus. 
     
     
         9 . The method of  claim 1 , wherein said treating or avoiding onset of a coronavirus infection comprises inhibition of tissue destruction by said coronavirus. 
     
     
         10 . The method of  claim 1 , wherein said composition is a pharmaceutical composition. 
     
     
         11 . The method of  claim 1 , wherein the compound is an inhibitor of coronavirus replication that has an IC50 value of at most 50 μM. 
     
     
         12 . The method of  claim 1 , wherein the composition is provided in a kit comprising comprised in a housing. 
     
     
         13 . The method of  claim 12 , wherein the composition further comprises a diluent and the kit comprises a container for the composition from which the composition is administered. 
     
     
         14 . The kit of  claim 13 , wherein the container is an inhaler. 
     
     
         15 . A method for identifying an inhibitor of coronavirus replication, the method comprising:
 a) contacting human colon carcinoma cells with a coronavirus in the presence of a candidate inhibitor of coronavirus replication,   b) determining virus replication in said human colon carcinoma cells a), wherein said determining virus replication comprises determining proliferation and/or viability of said human colon cancer cells by digital processing of pictures of unlabeled cells and/or quantification of stained nuclei,   c) comparing virus replication determined in b) to a reference, and   d) identifying an inhibitor of coronavirus replication based on a result of the comparing performed in step c).   
     
     
         16 . The method of  claim 15 , wherein said human colon carcinoma cells are CaCo-2 cells. 
     
     
         17 . The method of  claim 9 , wherein said inhibition of tissue destruction comprises inhibition of lung tissue destruction. 
     
     
         18 . The method of  claim 11 , wherein the inhibitor of coronavirus replication has an IC50 value of at most 25 μM. 
     
     
         19 . The method of  claim 11 , wherein the inhibitor of coronavirus replication has an IC50 value of at most 20 μM. 
     
     
         20 . The method of  claim 14 , wherein the composition is administered as an aerosol.